The objective of this pilot clinical trial is to obtain information on the tolerability, safety, and efficacy of a high potency combinatorial supplement in the treatment of Alzheimer disease (AD) in Down syndrome (DS). Individuals with DS have an increased incidence of AD and evidence of oxidative stress in brain. The DS population is an excellent candidate for antioxidant intervention. The trial will conform to a double-blind, placebo-controlled, and repeated analysis of variance design. The supplement will consist two cellular antioxidants (vitamins E 900 IU/day and C 200 mg/day) and a mitochondrial antioxidant (alpha-lipoic acid 600 mg/day). The clinical diagnosis of AD in DS will be made by the investigators utilizing their previous experience with DSM-IV criteria for dementia in DS. There are three specific aims: 1) to determine whether cognitive measures are improved by antioxidant supplementation. Outcome measures have been shown to have reliability and validity for DS. They comprise three informant scales (Dementia Rating Scale for Persons with Mental Retardation, Neuropsychology Behavior and Affect Profile, Vineland Adaptive Scales) and three direct assessments (Severe Impairment Battery, Brief Praxis Test, and the FULD-Object/Memory Test-modified); 2) to determine whether plasma biomarkers of lipid oxidative damage (malondialdehyde, isoprostanes), protein oxidative damage (carbonyl group formation), levels of beta-amyloid, and vitamin E levels will be altered in subjects receiving the diet; and 3) to determine the safety and tolerability of the antioxidant supplementation utilizing checklists for adverse events, clinical chemistries, and measures of medication compliance. All study measures will be obtained at baseline and at 6-month intervals for a total of 24 months of treatment. All study patients will be on an acetylcholinesterase inhibitor. Power analysis configured on the primary outcome measures supports a study group of 30 treated and 30 placebo randomized patients. Database management will facilitate analysis of the 24-month observations. The data from this study is intended to provide information relevant to the indications for a multicenter definitive clinical trial of antioxidants in DS. Since the process resulting in AD in DS is age dependent across the lifespan, a positive result from this pilot trial may have implications for utilizing high potency combinatorial antioxidants at earlier age epochs in DS. The pilot trial should also contribute information as to the possible role of antioxidants in the treatment or prevention of AD in the general population.